This study was conducted to evaluate the protective role of quercetin (Q) against the cytotoxicity, DNA damage and oxidative stress in rats fed aflatoxin (AFs)-contaminated diet. Female Sprague-Dawley rats were divided into six groups and treated for 21 days as follows: the control group; the group fed AFs-contaminated diet (1.4 mg/kg diet); the groups treated orally with Q at low or high dose (50 and 100 mg/kg b.w.) and the groups AFs-contaminated diet plus low or high dose of Q. At the end of experiment, blood and liver samples were collected for biochemical, histological, histochemical and genetic analyses. The results indicated that animal fed AFs-contaminated diet showed significant increase in serum biochemical parameters, oxidative stress markers and DNA fragmentation accompanied with significant decrease in total proteins, GPX, SOD, DNA and RNA content and fatty acid synthase (Fas) and TNFα gene expression in the liver tissue. Q at the two tested doses succeeded to normalize the biochemical parameters, improved the content of nucleic acids in hepatic tissues, the gene expression, the histopathological and histochemical picture of the liver. It could be concluded that Q has a potential antioxidant activity, a protective action and regulated the alteration of genes expression induced by AFs.